Monoclonal antibodies selectively bind tumor cell differentiation antigens in vitro and in vivo. We have devised methods of linking extremely toxic proteins to the antibodies to selectively kill tumor cells. (1) By cloning the toxins and mutating them to decrease non- target cell toxicity we have greatly increased the therapeutic specificity for tumor cells. (2) By the use of human cytotoxic proteins such as RNase linked to antibodies we have decreased the immune response of the recipient to the targeted toxins. 3) To improve this method of therapy of brain tumors we have prevented nonspecific toxicity to the vasculature by systemic delivery of chloroquine (4) We have developed new ways to target tumor cells to initiate programmed cell death. 5) We have explored the use of this technology to treat dystonia and muscle spasm disorders. - diphtheria toxin brain tumors immunotoxin monoclonal antibody ribonuclease RNases